Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits
Mostra el registre complet Registre parcial de l'ítem
- dc.contributor.author Brown, Andrew A.
- dc.contributor.author DIRECT Consortium
- dc.contributor.author Viñuela, Ana
- dc.date.accessioned 2023-11-02T07:26:28Z
- dc.date.available 2023-11-02T07:26:28Z
- dc.date.issued 2023
- dc.description.abstract We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue.
- dc.description.sponsorship The work leading to this publication has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement 115317 (DIRECT), resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. Information on the initiatives and activities of the IMI-DIRECT research consortium is available at https://directdiabetes.org.
- dc.format.mimetype application/pdf
- dc.identifier.citation Brown AA, Fernandez-Tajes JJ, Hong MG, Brorsson CA, Koivula RW, Davtian D, et al. Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits. Nat Commun. 2023 Aug 21;14(1):5062. DOI: 10.1038/s41467-023-40569-3
- dc.identifier.doi http://dx.doi.org/10.1038/s41467-023-40569-3
- dc.identifier.issn 2041-1723
- dc.identifier.uri http://hdl.handle.net/10230/58198
- dc.language.iso eng
- dc.publisher Nature Research
- dc.relation.ispartof Nat Commun. 2023 Aug 21;14(1):5062
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/115317
- dc.rights © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.keyword Data integration
- dc.subject.keyword Genetics
- dc.subject.keyword Genetics research
- dc.title Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion